Impact of frequency and duration of freeze-dried inactivated tissue culture hepatitis A vaccine (Aimmugen®) vaccination on antibody titers; a japanese cross-sectional study.

BACKGROUND: The effect of the timing of additional doses and the long-term persistence of lyophilized inactivated tissue culture hepatitis A (HA) vaccine (Aimmugen®) on antibodies is unknown. METHODS: A single-center, cross-sectional, observational study was conducted in collaboration with the Japan Air Self-Defense Force, whose personnel were immunized with Aimmugen® when deployed to endemic areas. Patients who consented to this study after a medical examination with blood sampling between June 2022 and February 2023 were included; HA-IgG level in the residual serum was measured using the chemiluminescent immunoassay method. The exact vaccination history was investigated based on immunization records maintained by the Ministry of Defense, and a questionnaire was used to collect confounding factors. RESULTS: Of the 181 participants observed, 49 were in the unvaccinated group, and 132 were in the vaccinated group. Out of the vaccinated group, 6.8 % received either one or two doses, 40.9 % received three doses, and 52.3 % received more than four doses. IgG antibody titers (S/CO value) in each group (0, 1 or 2, 3, and over 4) increased in a frequency-dependent manner, with those vaccinated over four times showing significantly higher IgG antibody titers than all other groups (0.19 ± 0.10 vs 3.66 ± 3.00 vs 7.63 ± 3.57 vs 10.57 ± 1.86, respectively). When the number of months elapsed from the last vaccination to the date of blood collection in each group was plotted against IgG antibody titer, the slope of the regression line flattened out from a decreasing trend in the order 1 or 2, 3, over 4. CONCLUSIONS: Three doses of Aimmugen® are efficacious, but four or more doses induce more robust and sustained antibody production. Additionally, four or more doses may be effective when there is a need to ensure long-term immunity or risk of prolonged exposure.

Performance of MALDI-TOF Mass Spectrometry in the Philippines.

Identification of the causative pathogen in infectious diseases is important for surveillance and to guide treatment. In low- and middle-income countries (LMIC), conventional culture and identification methods, including biochemical methods, are reference-standard. Biochemical methods can lack sensitivity and specificity and have slow turnaround times, causing delays in definitive therapy. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate diagnostic method. Most studies comparing MALDI-TOF MS and biochemical methods are from high-income countries, with few reports from LMIC with tropical climates. The aim of this study was to assess the performance of MALDI-TOF MS compared to conventional methods in the Philippines. Clinical bacterial or fungal isolates were identified by both MALDI-TOF MS and automated (VITEK2) or manual biochemical methods in the San Lazaro Hospital, Metro Manila, the Philippines. The concordance between MALDI-TOF MS and automated (VITEK2) or manual biochemical methods was analyzed at the species and genus levels. In total, 3530 bacterial or fungal isolates were analyzed. The concordance rate between MALDI-TOF MS and biochemical methods was 96.2% at the species level and 99.9% at the genus level. Twenty-three isolates could not be identified by MALDI-TOF MS. In this setting, MALDI-TOF MS was accurate compared with biochemical methods, at both the genus and the species level. Additionally, MALDI-TOF MS improved the turnaround time for results. These advantages could lead to improved infection management and infection control in low- and middle-income countries, even though the initial cost is high.

Refractory pharyngeal ulceration due to cytomegalovirus in a patient with HIV infection: a case report and literature review.

BACKGROUND: Cytomegalovirus (CMV) is an important pathogen among immunocompromised hosts. Typically, CMV in human immunodeficiency virus (HIV) infection causes diseases of the retina, digestive tract, lungs and liver, but there are few cases of CMV infection of the pharynx and larynx. CASE PRESENTATION: A 57-year-old man with HIV infection was admitted because of pharyngeal pain. Before and after admission, pharyngeal biopsies guided by laryngeal endoscopy were performed four times, but pathological examination showed nonspecific inflammation, and the cause of pharyngeal ulceration was unclear. Additionally, the ulceration deteriorated after initiation of retroviral therapy. Laryngomicrosurgery was conducted under general anesthesia to remove tissue, and pathological diagnosis confirmed CMV infection. Pathological features included enlargement of the cytoplasm and nucleus in infected cells, and intranuclear bodies called owl's eye inclusions. Ganciclovir dramatically improved the symptoms and laryngoscopic findings. CONCLUSIONS: This case was diagnosed as pharyngitis and pharyngeal ulceration caused by CMV infection, related to immune reconstitution inflammatory syndrome. In previous reports of CMV-induced pharyngeal or laryngeal ulceration in HIV infection, we found six cases similar to our present case. All cases were diagnosed by biopsy. The present case indicates the importance of biopsy for definitive diagnosis. CMV infection should be considered as a differential diagnosis of pharyngeal ulceration in patients with HIV infection.

Chagas disease: a report of 17 suspected cases in Japan, 2012-2017.

BACKGROUND: There are no reports on the prevalence of Chagas disease in Japan. Furthermore, screening programs and access to diagnosis and treatment have not been established. This study aimed to clarify the prevalence of Chagas disease among suspected cases in Japan and provide the reference data required for disease control. METHODS: Seventeen patients with suspected Chagas disease in Japan between 2012 and 2017 were included in the study. Patients were diagnosed with Chagas disease based on the two different serological tests for antibodies to Trypanosoma cruzi. Real-time polymerase chain reaction assay and blood culture techniques were performed to confirm T. cruzi parasitemia. RESULTS: Of the 17 patients, 11 (64.7%) were immigrants from Latin America. Ultimately, 6 patients (35.3%) were diagnosed with Chagas disease. Of these 6 patients, median age was 53.5 years, 5 patients were immigrants from Latin American, and 1 was Japanese who had a congenital infection. T. cruzi parasitemia was confirmed in 4 patients (66.7%), and 5 (83.3%) were in the chronic phase (Chagas cardiomyopathy, 4; megacolon, 1). Two patients (33.3%) commenced benznidazole treatment. CONCLUSION: Our study showed that some patients of Chagas disease living in Japan are already in the chronic phase at diagnosis because of substantial diagnostic delays. Further epidemiological studies on the prevalence of Chagas disease and systematic screening programs for the Latin American population are needed.

Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in ß-lactamase-negative ampicillin-resistant Haemophilus influenzae in Japan.

OBJECTIVE: ß-Lactamase-negative ampicillin-resistant Haemophilus influenzae is a common opportunistic pathogen of hospital- and community-acquired infections, harboring multiple single nucleotide polymorphisms in the ftsI gene, which codes for penicillin-binding protein-3. The objectives of this study were to perform comprehensive genetic analyses of whole regions of the penicillin-binding proteins in H. influenzae and to identify additional single nucleotide polymorphisms related to antibiotic resistance, especially to ampicillin and other cephalosporins. RESULTS: In this genome analysis of the ftsI gene in 27 strains of H. influenzae, 10 of 23 (43.5%) specimens of group III genotype ß-lactamase-negative ampicillin-resistant H. influenzae were paradoxically classified as ampicillin-sensitive phenotypes. Unfortunately, we could not identify any novel mutations that were significantly associated with ampicillin minimum inhibitory concentrations in other regions of the penicillin-binding proteins, and we reconfirmed that susceptibility to ß-lactam antibiotics was mainly defined by previously reported SNPs in the ftsI gene. We should also consider detailed changes in expression that lead to antibiotic resistance in the future because the acquisition of resistance to antimicrobials can be predicted by the expression levels of a small number of genes.

Cerebral Syphilitic Gumma in Immunocompetent Man, Japan.

Although cerebral syphilitic gummas are generally considered to be rare manifestations of tertiary syphilis, many reports exist of early cerebral syphilitic gumma. Our finding of cerebral syphilitic gumma in an HIV-negative man within 5 months after syphilis infection suggests that this condition should be considered in syphilis patients who have neurologic symptoms.

Efficacy of switching to dolutegravir plus rilpivirine, the small-tablet regimen, in patients with dysphagia: two case reports.

BACKGROUND: The advent of well-tolerated and effective anti-retroviral drugs against human immunodeficiency virus-1 (HIV-1) infection has been a major step forward that has achieved long-term survival in recent years. The number of HIV-1 infected patients who experience difficulty in swallowing tablets is expected to increase as the HIV-infected population advances in age or develops comorbidities or treatment sequelae affecting the central nervous system. CASE PRESENTATION: Here, we describe two HIV-1-infected patients who experienced progressive dysphagia leading to inability to swallow the antiretroviral tablets included in the standard regimen. Both patients had a plasma viral load < 40 copies/mL while receiving anti-retroviral therapy with the recommended combination antiretroviral therapy (cART) regimen, but the dysphagia necessitated a switch. By switching to much smaller sized combined regimen of dolutegravir (DTG) plus rilpivirine (RPV) tablets, both of our patients were able to successfully continue treatment and maintain adherence without the need for crushing tablets or preparing an oral suspension. Additionally, switching from the recommended cART regimen to DTG plus RPV successfully maintained viral suppression. At the last available follow-up (12 months after switching to DTG/RPV), HIV-1 viral load remained below the lower limit of quantification. CONCLUSIONS: An alternative therapeutic option that takes tablet size into consideration could not only contribute to improved patient adherence, but also a reduced care burden for HIV-infected patients with dysphagia. Thus, switching to the "small-tablet regimen" of DTG plus RPV has the potential to improve the survival and well-being of patients with dysphagia.

Development of a highly resolved loop-mediated isothermal amplification method to detect the N526K ftsI mutation of ß-lactamase-negative ampicillin-resistant Haemophilus influenzae.

Rapid and easy detection of sequence polymorphisms, including nucleotide point mutations of bacterial pathogens responsible for amino acid substitutions linked to drug resistance, is essential for the proper use of antimicrobial agents. Here, a detection method using loop-mediated amplification (LAMP) combined with amplification refractory mutation system (ARMS) to accurately distinguish a different single nucleotide in the target sequence was established, named ARMS-SNP LAMP. This procedure is capable of species-specific detection of a nucleotide (1578T) in the ftsI gene on Haemophilus influenzae without amplifying the sequence carrying the point mutations (T1578G/A) in ß-lactamase-negative ampicillin resistant (BLNAR) strains. Reactions were performed at 61°C for 45min. Successful target gene amplifications were detected by measuring real-time turbidity using a turbidimeter and visual detection. The assay had a detection limit of 10.0pg of genomic DNA per reaction and showed specificity against 52 types of pathogens, whereas amplifications were completely blocked in even 100.0ng/µL of genomic DNA with point mutations at T1578G and T1578A. The expected ARMS-SNP LAMP products were confirmed through identical melting curves in real-time LAMP procedures. This novel procedure was also used to analyze 57 clinical isolates of H. influenzae. All 25 clinical isolates with the naïve sequence of 1578T gave positive results. In addition, concordant negative results were obtained for 31 of the BLNAR strains with the T1578G mutation and one strain with the T1578A mutation. The ARMS-SNP LAMP method is a simple and rapid method for SNP-genotyping of a clinical isolate as point-of-care testing (POCT) technology. It is suitable for use in both resource-limited situations and well-equipped clinical settings because of its simplicity and convenience.

Clinical response to liposomal doxorubicin and rituximab in HHV-8-associated multicentric Castleman's disease in an HIV-positive patient.

We report a patient with HIV-associated multicentric Castleman's disease who had recurrent human herpesvirus-8 viremia associated with intermittent febrile exanthema and lymphadenopathy. Although the patient relapsed after single-agent treatment with liposomal doxorubicin, weekly infusions of rituximab led to complete remission even though the reactivation of the Kaposi's sarcoma was unfortunately observed. Rituximab could not only eliminate the accumulation of HHV-8 load but also play a part in the modulation of dysregulated CD20-positive B cells in HIV-associated multicentric Castleman's disease.

Chronic Chagas disease with advanced cardiac complications in Japan: Case report and literature review.

Due to the unprecedented recent increases in global migration, Chagas disease has become a global health threat and its epidemiology has drastically changed. Here we describe the first case in Japan of benznidazole treatment for chronic Chagas disease characterized by advanced cardiac complications. A 55-year-old Japanese-Brazilian woman who had previously presented with chronic heart failure was diagnosed as having Chagas disease and treated with benznidazole to prevent aggravation of her cardiac complications. However, benznidazole administration was stopped on day 56 due to severe drug-induced peripheral neuritis. Sixteen months later, her serologic test for Trypanosoma cruzi is still positive and she is being followed regularly by cardiology. Despite an estimated prevalence of over 4000 cases in Japan, only a few cases of Chagas disease have been reported. A Medline search revealed only 7 cases identified between 1995 and 2014 in Japan: in 6 cases, complications of chronic Chagas disease were apparent at the time of presentation, and sudden death occurred in 2 of these cases due to cardiac complications. This clinical case and literature review re-emphasize the urgent need to establish a surveillance network and improve the diagnostic methods and treatment framework for Chagas disease in Japan.

Human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient presenting with relapsing and remitting hyponatraemia.

We report a case of human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman's disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman's disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load.